The overall objective of this project is to identify and quantitate the factors that control FSH and LH secretion in men. Clinical studies will be directed principally toward inhibition of LH secretion by testosterone. In the previous years of this project testosterone inhibition of LH secretion in men with primary hypogonadism was shown to occur slowly, over the course of several weeks. In the next year the mechanism by which testosterone inhibits LH secretion will be studied in men with primary hypogonadism. In order to determine whether testosterone must be converted to dihydrotestosterone as estradiol in order to inhibit LH secretion, drugs that block the conversion of testosterone to dihydrotestosterone or estradiol will be administered to men with primary hypogonadism along with testosterone. Failure of serum LH to decrease at the same rate that it decreases when only testosterone is administered will be evidence for the inhibition of the conversion of testosterone to an active metabolite. Animal studies will focus on GnRH secretion by rat hypothalami and on a search for "inhibin". GnRH secretion will be studied in isolated rat hypothalami, incubated for short periods. After optimal incubation conditions are established (pH, glucose concentration, etc.), the effect of various hormonal manipulations will be studied. "Inhibin", the proposed substance from the seminiferous tubules that inhibits FSH secretion will be sought in canine sertoli cell tumors. Steroid-free extracts of these tumors will be tested by inhibition of immunoassayable FSH secretion in castrated male rats and by inhibition of HCG-stimulated ovarian weight gain in immature female rats.